| 王炉依,陈灵吉,楼丽华,邢政.抗体偶联药物德曲妥珠单抗在晚期乳腺癌中的研究进展[J].浙江中西医结合杂志,2024,34(9): |
| 抗体偶联药物德曲妥珠单抗在晚期乳腺癌中的研究进展 |
| Research progress of the antibody-coupled drug trastuzumab deruxtecan in advanced breast cancer |
| 投稿时间：2023-09-03 修订日期：2024-06-21 |
| DOI： |
| 中文关键词: 抗体偶联药物 德曲妥珠单抗 人表皮生长因子受体2 晚期乳腺癌 |
| 英文关键词:Antibody drug conjugates Trastuzumab deruxtecan Human epidermal growth factor receptor 2 Advanced breast cancer |
| 基金项目:全国名老中医药专家传承工作室建设项目(国中医药人教发[2014]20号);浙江省国医名师传承工作室建设项目(浙中医药[2021]18号,GZS2021006) |
|
| 摘要点击次数: 868 |
| 全文下载次数: 2 |
| 中文摘要: |
| 根据世界癌症发病率统计，乳腺癌已超越肺癌成为女性中发病率居于首位的癌症。在乳腺癌患者中，人表皮生长因子受体2(human epidermal growth factor receptor2，HER2)阳性患者为15%~20%[1]，HER2阳性定义为免疫组化（immunohistochemistry，IHC）分析得分为3+或IHC2+而原位杂交（in situ hybridization, ISH）为阳性。HER2靶向药物如曲妥珠单抗、帕妥珠单抗等进入临床后，显著延长了HER2阳性乳腺癌的生存期，改善了疾病预后，HER2阳性不再是预后不良的标志[2]。
抗体偶联药物（antibody-drug conjugate, ADC）具有抗体药物的肿瘤靶向性，特异性地将细胞毒性药物运输到目标癌细胞，降低了细胞毒性药物暴露的全身毒性，增强了抗肿瘤活性。基于先前接受曲妥珠单抗和紫杉烷治疗的HER2阳性晚期乳腺癌患者的总体生存数据，曲妥珠单抗-美坦新偶联物(恩美曲妥珠单抗（Trastuzumab Emtansine，T-DM1）)是首个获得美国食品和药物管理局(food and drug administration, FDA)批准用于乳腺癌的ADC，于2013年上市。T-DM1由曲妥珠单克隆抗体和微管蛋白聚合抑制剂美坦新(DM1)通过硫醚连接剂偶联组成，可选择性向肿瘤细胞输送细胞毒药物，T-DM1的低膜渗透性使细胞毒药物无法到达邻近的HER2低表达细胞而表现出旁观者杀伤作用[3] 。
T-DM1的获得性耐药、对HER2低表达肿瘤细胞缺乏杀伤效应等局限，促使了下一代ADC德曲妥珠单抗（Trastuzumab Deruxtecan，T-DXd）的开发，由曲妥珠单抗和拓扑异构酶I抑制剂组成，本文就T-DXd在晚期乳腺癌中的安全性和有效性的临床数据进行综述。 |
| 英文摘要: |
| Antibody-drug conjugates are composed of a monoclonal antibody carrier, a cytotoxic agent (payloads), and a cleavable or noncleavable linker. Trastuzumab deruxtecan is a next-generation antibody-drug conjugate, which belongs to the spectrum of antibody-drug conjugate, consisting of f a monoclonal anti-HER2 antibody and a topoisomerase I inhibitor(DXD). For HER2-positive advanced breast cancer patients with disease progression who have received trastuzumab Emtansine in the past, trastuzumab deruxtecan has shown superior disease remission and control rate, improving survival time. In addition, it also brings survival benefits to patients with advanced breast cancer with human epidermal growth factor receptor2 low-expression, which may be a new hope for patients with metastatic breast cancer with low expression. Phase 3 clinical trials demonstrated that the antitumor activity of trastuzumab deruxtecan was superior to Trastuzumab Emtansine in human epidermal growth factor receptor2-positive advanced breast cancer patients, and that the antitumor activity of trastuzumab deruxtecan in human epidermal growth factor receptor2 low-expression advanced breast cancer patients was superior to the doctor-selected treatment regimen (capecitabine combined with trastuzumab or lapatinib). Drug related hematological toxicity, interstitial lung disease and other safety issues have also attracted extensive attention, especially interstitial pneumonia may limit the clinical use of trastuzumab deruxtecan. This review reviews the clinical data on the safety and efficacy of trastuzumab deruxtecan in advanced breast cancer. |
| 查看全文 查看/发表评论 下载PDF阅读器 |
| 关闭 |
|
|
|
